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International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy

Carelli, Valerio MD, PhD; Carbonelli, Michele MD; de Coo, Irenaeus F. MD, PhD; Kawasaki, Aki MD; Klopstock, Thomas MD; Lagrèze, Wolf A. MD; La Morgia, Chiara MD, PhD; Newman, Nancy J. MD; Orssaud, Christophe MD; Pott, Jan Willem R. MD, PhD; Sadun, Alfredo A. MD, PhD; van Everdingen, Judith MD; Vignal-Clermont, Catherine MD; Votruba, Marcela MD, PhD; Yu-Wai-Man, Patrick MD, PhD; Barboni, Piero MD

doi: 10.1097/WNO.0000000000000570
Original Contribution

Abstract: Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000–45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone–Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

IRCCS Institute of Neurological Sciences of Bologna (VC, MC, CLM), Bellaria Hospital, Bologna, Italy; Unit of Neurology (VC, CLM), Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Department of Neurology (IFdC), Erasmus Medical Center, Rotterdam, the Netherlands; Neuro-Ophthalmology Unit (AK), University of Lausanne, Jules Gonin Eye Hospital, Lausanne, Switzerland; Department of Neurology (TK), Friedreich-Baur-Institute, Ludwing-Maximilians-University, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy) (TK), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (TK), Munich, Germany; Eye Center (WAL), Medical Center, Faculty of Medicine, University of Freiburg, Breisgau, Germany; Departments of Ophthalmology, Neurology and Neurological Surgery (NJN), Emory University School of Medicine, Atlanta, Georgia; Department of Ophthalmology (CO); Referral Center for Rare Diseases OPHTARA, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Ophthalmology (JWRP), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Doheny Eye Institute (AAS), Los Angeles, California; Department of Ophthalmology (AAS), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Neuro-ophthalmology (JvE), The Rotterdam Eye Hospital, Rotterdam, the Netherlands; Rotterdam Ophthalmic Institute (ROI) (JvE), Rotterdam, the Netherlands; Fondation Ophtalmologique Adolphe de Rothschild (CV-C), Paris, France; School of Optometry and Vision Sciences (MV), Cardiff University, and Cardiff Eye Clinic, University Hospital of Wales, Cardiff, United Kingdom; Wellcome Trust Center for Mitochondrial Research (PY-W-M), Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom; Newcastle Eye Center (PY-W-M), Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom; NIHR Biomedical Research Center at Moorfields Eye Hospital and UCL Institute of Ophthalmology (PY-W-M), London, United Kingdom; Department of Clinical Neurosciences (PY-W-M), School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Ophthalmology (PB), San Raffaele Scientific Institute, Milan, Italy; and Studio Oculistico d'Azeglio (PB), Bologna, Italy.

Address correspondence to Valerio Carelli, MD, PhD, IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Via Altura 3, 40139 Bologna, Italy; E-mail: valerio.carelli@unibo.it

The funding organizations (San Raffaele Institute and Santhera Pharmaceuticals) provided reimbursement for travel, but no compensation was given to any of the participants. Santhera Pharmaceuticals provided an unrestricted research grant, but the company had no role in the choice and involvement of scientific leaders and members of the jury or in the preparation, review, or approval of the final list of consensus statements. Content Ed Net, Rome, Italy, provided support to the logistics and organization of the meeting, which was funded by Santhera Pharmaceuticals.

Before initiation of this Consensus conference, scientific leaders and all members of the jury were required to complete conflict of interest statements. None of the experts had disqualifying conflicts of interest. With reference to authors of this paper: V. Carelli has a consultancy agreement and is the PI of clinical trials sponsored by GenSight Biologics and Santhera Pharmaceuticals, and has received travel reimbursements and speaker honoraria from Santhera Pharmaceuticals; M. Carbonelli is an investigator in clinical trials sponsored by Gensight Biologics and Santhera Pharmaceuticals; T. Klopstock has received research grants, travel reimbursements, speaker and consultancy honoraria from Santhera Pharmaceuticals and GenSight Biologics; W. Lagrèze has a consultancy agreement with Santhera Pharmaceuticals and has received speaker honoraria from Santhera Pharmaceuticals; C. La Morgia has received travel reimbursements and speaker honoraria from Santhera Pharmaceuticals and is an investigator in clinical trials sponsored by Gensight Biologics and Santhera Pharmaceuticals; N. J. Newman has a consultancy agreement with GenSight Biologics and Santhera Pharmaceuticals and is the PI of clinical trials sponsored by Gensight Biologics; C. Orssaud has a consultancy agreement with Santhera Pharmaceuticals; A. Sadun has a consultancy agreement and is the PI of clinical trials sponsored by Gensight Biologics and Stealth Peptides; J. van Everdingen has no disclosures; C. Vignal-Clermont has a consultancy agreement and is the PI of clinical trials sponsored by Gensight Biologics; M. Votruba is an investigator in clinical trials sponsored by Santhera Pharmaceuticals; P. Yu-Wai-Man has a consultancy agreement with GenSight Biologics and is the PI of clinical trials sponsored by Gensight Biologics and Santhera Pharmaceuticals; P. Barboni has a consultancy agreement with Santhera Pharmaceuticals, has received travel reimbursements and speaker honoraria from Santhera Pharmaceuticals, and is an investigator in clinical trials sponsored by GenSight Biologics. The remaining authors report no conflicts of interest.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the San Raffaele Scientific Institute.

© 2017 by North American Neuro-Ophthalmology Society